We report a case of a 53-year-old man with early stage (stage II) avascular necrosis (AVN) of the femoral head treated with pulsed radio frequency (pRF) of articular branches of femoral and obturator nerves with autologous platelet-rich plasma (PRP) intra-articular injection. Autologous PRP was injected into the diseased hip under fluoroscopy guidance. The patient was followed up at 1, 4, and 12 weeks after treatment, together with visual analog scale (VAS) Walking Index, Harris Hip Score, and Range of Motion (ROM) assessments. The patient's severe hip pain considerably improved during subsequent follow-up at 1, 4, and 12 weeks after treatment, with significant improvement in VAS pain scores, Harris Hip Score, and ROM. This case represents the first evidence of complete resolution of symptoms of stage II AVN of the hip, following a combination treatment with pRF with PRP having a synergistic beneficial effect.

A 53-year-old patient presented with severe (walking visual analog scale [VAS] score of 8/10) pain in the right hip. No history of trauma was reported. Pain was constant and nonprogressive. He gave a history of fall from 15 feet, 15 years back, no fracture reported, and recovered fully in 3–4 days. Since then, he had mild pain. But pain increased since last 1 year. Pain increased on walking a few steps. No history of surgery or any other treatment for this pain was reported. On examination, limping gait was observed. On palpation, there was no tenderness. On testing the Range of Motion (ROM) assessment of hip, internal rotation was found to be painful and limited to 10° on right side. X-ray Hip was grossly normal [Figure 1]. He underwent MRI of the bilateral hip joint. It showed Stage II Ficat and Arlet [Table 1] bilateral avascular necrosis of the femoral head with maintained head architecture [Figure 2] and [Figure 3].

No history of any steroid or alcohol intake was reported. The patient was on and off nonsteroidal anti-inflammatory drug, tramadol, vitamin D, and calcium supplements. As the deformity was not severe, surgical treatment was ruled out. Because of his incapacitating pain, he was referred to the pain clinic. The patient was counseled for treatment with pulsed radio frequency (pRF) and autologous platelet-rich plasma (PRP) treatment for the right hip, and he consented for the same.

Procedure

The patient was treated first with pRF and thereafter autologous PRP injection in the same session.

pRF of articular branches of femoral and obturator nerves supplying right hip joint was done. The patient was placed in supine position. The area for injection was prepared and draped. Local anesthesia infiltration was carried out with 2% Xylocaine. A 22G long 10-mm active tip Neurotherm RF cannula, Wilmington, MA, USA, was inserted at desired locations for lesioning of articular branches of femoral and obturator nerves [Figure 4] and [Figure 5].

Figure 4: Nerve supply of the hip joint–articular branches of the femoral and obturator nerves. L suggests left side of patient i.e. procedure was done on right hip joint

Using NeuroTherm, Smith and nephew, Inc Andover, MA, 01810, USA, Generator, sensory (50 Hz) stimulation was performed to achieve good stimulation of the painful area. Motor stimulation (2 Hz) was performed to rule out if leisioning is involving any motor component. Impedance was noted and was in the range of 250–300 ohm. Once the satisfactory stimulation was achieved, pRF was carried out at 42°C for 240 s at each point.

Autologous PRP therapy: The patient was placed in the supine position. A total of 4 mL anticoagulant citrate dextrose solution, solution A (ACD-A) was collected in the syringe and mixed with 30 mL blood that was collected from cubital vein. The REV-MED TriCell Platelet Plasma Product Kit (Bosham 8EX United Kingdom) and the Fleta-40P (Hanil Science Inc, Gimpo 10136, Korea) multipurpose centrifuge were used for autologous PRP preparation. A total of 4 mL PRP buffy coat was collected after processing as per the company instructions in a 5-mL syringe. Right hip under fluoroscopic view was localized. The local anesthetic infiltration was performed with Xylocaine (2%) and the 23G spinal needle was then inserted so that the tip touches the bone of the neck, which ensures that it has passed through the capsule of the hip joint. Contrast medium Omnipaque containing Iodine 300mg/ml (GE Healthcare, Shanghai, China) was then injected to see the spread of contrast in the intra-articular space. Initially the position for the tip was not correct, the dye was not seen spreading around the neck and in the hip joint. The dye spread is not seen in the joint. ([Figure 6] - Red arrows), the needle is relocated until good spread is obtained ([Figure 6] - Blue arrows). If wrongly positioned, the needle is relocated until good spread is obtained. After confirming proper location, 4mL of autologous PRP was injected slowly [Figure 6]. The needle was removed and dressing was applied.

Figure 6: Needle in the joint with improper spread of the contrast (red arrow) and after relocating the tip, showing proper spread of the contrast (blue arrow)

Pre-procedure pain was 8/10; ROM in internal rotation was only possible by 10°. At 1 week, the pain was 3/10, his ROM improved significantly to 35°. At 4-week, the patient had VAS 2/10 and was able to do all his activities with very minimal discomfort. ROM was maintained at 30° and was free with minimal pain. At 12-week, the patient had VAS 1–2/10 (occasional pain on climbing stairs), his ROM was free without pain.

Harris Hip scores at pre-procedure, 1, 4, and 12 weeks post-procedure were 10 (moderate to severe problem), 38, 42, and 42, respectively. Very significant improvement was observed in the function and pain. The patient was able to walk without much discomfort for 20–25 min. Limping of the gait also improved to almost normal walk.

Discussion

AVN, also known as osteonecrosis, is defined as cellular death of bone components because of interruption of the blood supply, and occurs most commonly in the hip.[1]

The prevalence of AVN of the femoral head is unknown. There are an estimated 15,000–20,000 new cases in the US each year and 2,500–3,300 cases in Japan.[2]

The etiology includes (from most common to less common): steroids (most common), idiopathic (second most common), alcohol, trauma, pregnancy, drug induced, and aplastic anemia.[3]

The mechanism associated with AVN may include trauma, venous occlusion, vessel wall injury, fat embolism, microfracture from trabecular insufficiency, interosseous hypertension, interosseous hemorrhage, vasculitis, and intravascular coagulation. The pathological findings include empty lacunae in the osseous matrix and necrotic bone marrow of trabecular interstices. There are reparative tissues around the necrosed part of AVN. Unfortunately, the healing process is not good enough to overcome the necrotic process, which results in more necrosis of the bone.[3]

The surgical option includes total hip replacement (THR), which is the only definitive cure for AVN of the hip, but has its own several drawbacks. These include failure of implants after some years (usually approximately 15 years), a prolonged period of postoperative recovery, and physical therapy.[4]

There are several clinical studies that showed good results in treating hip AVN with bone marrow–derived mesenchymal stem cells (MSCs) or adipose tissue–derived stem cells (ASCs),[3],[5],[6] with PRP[7] with or without ASCs. Very few reports on the use of pRF in AVN are available. No reports in the literature, which use pRF and PRP in combination are reported. We used these two techniques as both work by different mechanism and thereby, we have synergistic effect of regeneration and pain relief.

The RF signal on the electrode produces two types of basic fields in the tissue: electrical fields and magnetic fields. The current produces ionic friction and heat, and this then produces the increase in temperature around the electrode tip. When the electrical field becomes high enough, it may produce modifications of neural structures and neuronal behavior. Kothari in his article has thrown light on few newer concepts and probable mechanisms of pRF, which include anti-inflammatory effect and generalized effect on immune cells and immune system.[8] Reports of five cases of intra-articular application of pRF with good pain relief are available.[8] All of these mechanisms might be relevant in understanding how RF leisioning produces its effects in pain relief therapy. The fact that the application of pRF in the joint space (intra-articular) can produce pain relief suggests that one of the mechanism of pain relief in pRF may be its influence on the immune system.[8],[9] There are other theories such as increased c-fos expression in the dorsal horn and the long-term depression of the higher afferent synapses, which could not be proven till date.[8],[9]

Chye et al.[10] treated 29 patients with chronic hip pain, which were divided into two groups (pRF and conservative treatment). Fifteen patients were treated with pRF of the articular branches of the femoral and obturator nerves, and 14 patients were treated with the conservative treatment. VAS, Oxford Hip Scores, and pain medications were used for outcome measurement before treatment and at 1, 4, and 12 weeks after treatment. They concluded that compared to conservative treatment, pRF of the articular branches of the femoral and obturator nerves provides greater pain relief for chronic hip pain and also aids in physical functioning.[10]

Autologous PRP is now commonly used regenerative therapy in many patients with orthopedic degenerative and sports injury apart from many other conditions. There is a huge interest in regenerative treatments such as PRP and stem cells to repair the damaged tissues. Platelets are responsible for storing intercellular mediators and cytokines, which release their α-granule content after aggregation. This process is intense in the 1st h, and the synthesis of cytokines and growth factors continues almost up to 7 days. In newer commercial systems, adding collagen, calcium, and thrombin, glass contact, or freezing cycles, help to activate platelets.[6]

In PRP, the red blood cells are reduced to <5% and platelet concentration is increased to more than 94%. Platelets are the storehouse of a number of powerful growth factors. In a healthy individual, a normal platelet count is between 150,000 and 450,000 cells/μL of blood. The general consensus among most studies suggested that effective concentration of platelet in PRP should be a minimum increase of five times the normal concentration of platelets (approximately 1 million platelets/μL).[6]

Andriolo et al.[11] published the study to document the available evidence on the use of regenerative techniques for the treatment of AVN. They also wanted to understand their benefit compared to core decompression (CD) alone in avoiding failure and the need for THR. They searched three medical electronic databases according to preferred reporting items for systematic reviews and meta-analyses guidelines. Forty-eight studies were included in this systematic review. These studies reported the results of different types of regenerative techniques: MSC implantation in the osteonecrosis area, intra-arterial infiltration with MSCs, implantation of bioactive molecules, or PRP. They reported good overall results. The cumulative survivorship was 80% after 10-year follow-up. The results were better when regenerative treatments were combined to CD compared to CD alone (89.9% vs. 70.6%, P < 0.0001). They concluded that regenerative therapies offer good clinical results for the treatment of AVN.[11]

Tinnirello et al.[12] treated 14 patients with pRF of articular branches of femoral and obturator nerves. Eight patients (57%) reported >50% pain relief and improved disability score at 6-month follow-up. Three patients (21%) maintained this improvement at 12 months. They concluded that pRF is a safe and effective modality to treat hip joint pain in the short and medium term.[12]

In this case, we combined these two modalities to have synergistic effect. As both have different mechanisms, we hypothesize that combining these two modalities may prove beneficial for patients with moderate-to-severe AVN.

Conclusion

The combination therapy resulted in very good improvement in patient's pain, function, and ROM. This significant improvement in this patient suggests that research on combine therapy (pRF + autologous PRP) is definitely a possibility to know its beneficial effects. Larger numbers of patients need to be evaluated to better understand the efficacy of the combined pRF and PRP therapy on patients with AVN.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.

Ninomiya S. An epidemiological survey of idiopathic avascular necrosis of the femoral head in Japan: annual report of Japanese Investigation Committee for Intractable Disease. Osaka, Japan: University Publisher; 1989.